1. Field of the Invention.
This invention relates to techniques and implements to facilitate the attachment of cells to a surface, and more specifically relates to an apparatus for plasma treating the lumen wall of a small diameter tube in preparation for cell deposition.
2. Background.
Over the past three decades, vascular grafts have been used extensively to restore blood flow to areas of ischemia, to provide blood flow for hemodialysis patients and for repair of arterial aneurisyms. Such procedures are generally initially successful, but long term prognosis for patients receiving small diameter grafts is not encouraging, principally because grafts of 4 mm or less become occluded over time due to the thrombogenic nature of the graft material.
Extensive investigations have been carried out in attempts to find blood compatible materials for vascular grafts and other biomedical devices. Synthetic plastics are the preferred materials, but even such plastics as polytetrafluoroethylene and the silicone rubbers which are more compatible with blood than most plastics still show thrombogenic characteristics.
The problems of thrombogenicity and occlusion are exacerbated with small diameter grafts. Van Wachem et al., in Biomaterials 6, 403 (1985) reported clinical success with polymeric grafts of greater than 4 mm, but that grafts of less than 4 mm gave generally disappointing clinical results due to immediate occlusion. Likewise, Baker et al., in American Journal of Surgery 150, 197 (1985) stated that long term patency of large diameter vascular grafts is relatively acceptable, but small diameter (less than 5 mm) grafts exhibit poor long-term patency rates.
The ideal blood surface interface has long been considered to be the naturally occurring human endothelium, and much current research centers on endothelialization procedures. For example, seeding of 4 mm ID diameter polyester vascular grafts with endothelial cells and patency after implantation in dogs is discussed by Belden et al., in Trans. Am. Soc. Artif. Intern. Organs. 28, 173 (1982).
Jarrell et al. (Annals of Surgery, 203, 671 (1986)) disclosed a high percentage of firm adherence of endothelial cells to polyester coated with platelet rich-plasma in 10 min., to amnion/collagen coated polyester in 30 min. and to plain polyester in two hours, but that only the amnion/collagen coated surface exhibited complete graft coverage.
Modification of polymeric surfaces by treatment with a variety of plasmas to accomplish various purposes is well known. The term "plasma" is used generally to describe the state of ionized gas. A plasma consists of high energy positively or negatively charged ions, negatively charged electrons as well as neutral species. As known in the art, a plasma may be generated by combustion, flames, physical shock or most often by electrical discharge, such as a corona or glow discharge. In radiofrequency (RF) discharge, a substrate to be treated is placed in a vacuum chamber and gas at low pressure is bled into the system. The gas is subjected to an RF electrical discharge, either capacitive or inductive, which generates an electromagnetic field. Ionization of the gas takes place as a result of absorption of energy from the field giving high energy particles which modify the surface of the substrate.
The extent of substrate surface modification by a plasma is a function of the number and average energy of the particles striking the surface. The energy of charged particles in a plasma is best defined by the ratio (E/p) of the electric field strength E to the background gas pressure p. This ratio is a relative measure of the average energy that an ion or electron can gain between successive scattering collisions with neutral gas molecules. It is evident from the ratio that the energy of a plasma particle can be increased by either increasing the field strength or decreasing the gas pressure. Field strength may be increased by increasing the power of the electrical discharge; this, however, is accompanied by additional heat formation. On the other hand, if the gas pressure is reduced too far, insufficient molecules are present for ionization.
Plasmas have been used to alter surface wettability, static properties and receptivity of a surface to deposition of a layer of an adherent polymeric material. Japanese Patent No. 122529 discloses preparing a surface for graft polymerization by placing a tube in an insulating sheath, activating an inner surface of the tube with an inductively generated plasma and exposing the surface to a polymerizable monomer.
Van Wachem et al., (supra) discloses that endothelial cells can be cultured on glass or glow-discharge treated polystyrene.
Garfinkle et al., in Trans. Am. Soc. Artif. Intern. Organs, 30, 432 (1984) discloses plasma deposition of a fluorocarbon polymer coating onto the luminal surface of 4-5 mm inside diameter porous polyester grafts. In this report, an inductive plasma generated externally of the graft penetrates to the lumen by passing through the pores of the graft. Markedly improved patency for the treated grafts is reported.
Published European Patent Application EP 89-124A discloses plasma treatment of the inside of a plastic tube of 3.5 mm inside diameter by inserting the tube inside an insulating second tube and positioning the electrodes outside of the insulating tube.
In spite of the extensive investigations on antithrombogenic prosthetic devices, the problem of thrombogenicity has not been satisfactorily solved, in particular with respect to small diameter grafts. It is toward the solution of this problem that the current invention is directed.